Scientists around the world have been working at a record speed to develop vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the virus responsible for coronavirus disease 2019 (COVID-19).
Several of these vaccines have received emergency use authorization (USA) from numerous regulatory bodies, which has led to the initiation of vaccination programs in many countries around the world. One of the approved messenger ribonucleic acid (mRNA) based vaccines is BNT162b2, which has been reported to be highly effective against symptomatic COVID-19 disease.
To study: Long-term immunogenicity of BNT162b2 vaccination in the elderly and younger health care workers. Image credit: Yuganov Konstantin / Shutterstock.com
Background
Recent studies have revealed that vaccine-induced antibodies remained stable for about six months. To date, all vaccines received in the US have been developed against the spike (S) protein of the original SARS-CoV-2 strain.
Due to the ability of this virus to mutate frequently, several variants of SARS-CoV-2 have appeared. These variants have been classified as variants of interest (VoI) and variants of interest (VoC) according to their virulence and speed of transmission.
The emergence of SARS-CoV-2 variants, especially the Delta variant, has called into question the efficacy of many vaccines. Scientists have revealed that vulnerable groups such as the elderly who have been vaccinated using the BNT162b2 vaccine have a higher risk of contracting the SARS-CoV-2 Delta variant compared to younger adults.
Many studies have reported an increase in the rate of COVID-19, especially due to the dominant circulating Delta strain, in highly vaccinated populations. These reports have prompted authorities in several countries, including the United States, Israel and Germany, to discuss the effectiveness of a third dose of booster in populations of vulnerable patients, such as those over 60 years of age.
A new study
Since the maintenance of vaccine-induced immunity in the elderly is unclear, a new cohort study comparing immune responses between vaccinated seniors and health care workers (HCWs) has been conducted. The authors of this study, which is available on the web medRxiv * prepress server, determined immune responses six months after the first vaccination with BNT162b2.
In this study, six-month follow-up visits were completed for 107 HCWs, whose mean age was estimated to be 35 years, as well as 82 elderly people with a mean age of 82.5 years. In both study groups, women were in the majority.
The authors of this study excluded participants who contracted COVID-19, as confirmed by the reverse transcriptase polymerase chain reaction (RT-PCR), after receiving the first or second dose of the BNT162b2 vaccine.
Study results
The current study revealed that rates of anti-SARS-CoV-2 S1-immunoglobulin G (IgG) seropositivity decreased in the elderly age group compared to the HCW group six months after vaccination. The researchers also found that the reduction in anti-RBD and anti-full S-IgG levels in the sera of the elderly group was more pronounced than in the HCWs. The current study also reports a significant decrease in surrogate virus neutralization (sVNT) titers among the elderly by 56% compared to 88.1.
In the current study, the researchers used the pseudovirus neutralization test (pNT) to determine the neutralization of the Delta variant after vaccination. They revealed a substantial decrease in serum neutralization of the Delta variant two months after subjects received the first dose of vaccine and four weeks after the second dose.
In 60.6% of the vaccinated elderly group, serum neutralization of the Delta variant was observed six months after vaccination. However, this was not the case for the younger study group containing HCW, where 95.2% of the HCW cohort could neutralize the same variant six months after vaccination.
This study also evaluated the neutralization of the Alpha variant in the same cohorts. To this end, 95.2% of HCWs and 69.0% of the elderly cohort could neutralize the Alpha variant six months after complete BNT162b2 vaccination. As expected, the mean neutralizing titers for the Alpha and Delta variants were significantly reduced in the older group compared to the younger HCWs.
(A) Anti-SARS-CoV-2 N, (B) RBD- (C) and full-tip IgG measured in HCW serum and elderly people vaccinated with BNT162b2 six months after the first vaccination. (D) The neutralization capacity was measured by sVNT and (E) serum neutralization against Alpha (B.1.1.7) VOC detected by pNT in HCW and vaccinated elderly six months after the first vaccination. (F) Ability to bind serum IgG against six different RBDs of SARS-CoV-2 variants carrying the indicated mutations in HCW and elderly, as measured by ELISA. Dashed lines indicate the manufacturer’s threshold values: for anti-N, anti-RBD and anti-spike IgG ≥1 S / Co, for sVNT> 30% and the lower limit of detection (1:10 dilution) for pNT. The lines indicate the mean and the interquartile range, except the pNT, where the geometric mean and the 95% confidence interval are shown. P values were calculated using the non-parametric Mann Whitney U test or the Kruskal-Wallis test with the Dunn multiple comparison test. S / Co: cut signal, N: nucleocapsid protein, RBD: receptor binding domain, sVNT: surrogate virus neutralization test, ACE2: angiotensin 2 converting enzyme, ID50: 50% inhibition dilution.
The scientists observed that the appearance of viral variants containing mutations such as E484K, which cause evasion of vaccine-induced immune responses or immune responses due to natural COVID-19 infection, would further reduce immunity among the old age group. .
In the elderly group, the researchers found a reduction in the binding capacity of serum antibodies to RBDs containing mutations such as K417N / T, L425R, T478K, E484K / Q, N501Y, and E484Q. These mutations are present in six known variants of SARS-CoV-2, indicating that the vaccinated elderly group is still highly susceptible to COVID-19.
However, this reduction in binding capacity was not observed in the HCW cohort. Current research also revealed a reduction in SARS-CoV-2-S1 T cell reactivity in the elderly compared to HCWs.
Conclusion
The authors of the current study indicated a significant decrease in COVID-19 vaccine-induced immune responses in the elderly. However, neutralizing capacity was still detected after six months of initial vaccination in the younger group of HCW.
This study showed a significant reduction in immunogenicity markers in the elderly six months after vaccination. It also provided evidence that a two-dose vaccination regimen induces a less stable immune response in the older age group compared to younger groups.
* Important news
medRxiv publishes preliminary scientific reports that are not reviewed by experts and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.